Ready-to-use parenteral amiodarone: a feasibility study towards a long-term stable product formulation. Issue 2 (13th April 2016)

• Record Type: Journal Article
• Authors: Jacobs, Maartje S; Luinstra, Marianne; Moes, Jan Reindert; Chan, Tiffany C Y; Minovic, Isidor; Frijlink, Henderik W; Woerdenbag, Herman J
• Is Part Of: European journal of hospital pharmacy. Volume 24:Issue 2(2017)
• Page Start: 110
• Page End: 114
• Publication Date: 2016-04-13
• Subjects: intravenous amiodarone -- pharmaceutical formulation -- ready-to-use -- cyclodextrins -- sulfobutylether-beta-cyclodextrin; Pharmacy -- Periodicals; Hospital pharmacies -- Periodicals; 615.1
• DOI: 10.1136/ejhpharm-2015-000860
• Languages: English
• ISSNs: 2047-9956

Abstract

Abstract : Objectives: To determine the feasibility of preparing a long-term stable ready-to-use parenteral amiodarone formulation using cyclodextrins as dissolution enhancer. Methods: A preformulation study was performed with different molar ratios of hydroxypropyl-beta-cyclodextrin (HP-BCD) or sulfobutylether-beta-cyclodextrin (SBE-BCD) to amiodarone in order to investigate enhancement of amiodarone's water solubility. Further, effects of pH and temperature on the dissolution rate during production were investigated. Shelf-life was determined for a ready-to-use iso-osmotic preparation of 1.8 mg/mL amiodarone with SBE-BCD in a molar ratio of 1:3. Amiodarone content was assessed using a validated high-pressure liquid chromatography ultraviolet method. Results: Amiodarone–SBE-BCD in a molar ratio of 1:3 at pH 4.0–5.0 yielded the best results in terms of increased solubility and dissolution time (90 min). With SBE-BCD, a smaller molar ratio to amiodarone was needed than with HP-BCD. The amiodarone content of the final formulation stored 12 months at 21°C in daylight remained unchanged. Conclusions: A ready-to-use or ready-to-administer amiodarone product, prepared in a hospital pharmacy, for intravenous application in an acute clinical setting is a feasible option from a chemical, physical and microbiological point of view. The availability of such a product will have a significant impact on medication safety, and production should therefore be considered.